Angiotensin receptor blockers (ARBs) selectively inhibit the binding of angiotensin II (ANG II) to angiotensin II type 1 (AT1) receptors.1-5
The renin-angiotensin system (RAS) regulates blood pressure and fluid electrolyte balance.2,6-8 Uncontrolled RAS leads to the development of hypertension and congestive heart failure.2,6-9 Angiotensin II (ANG II) is the primary hormone that mediates increased vasoconstriction, cardiac contractility, and cardiac, renal, and vascular hypertrophy, stimulates adrenal aldosterone secretion, and increases renal tubular sodium absorption.6-8 Increased aldosterone can increase reabsorption of sodium and the excretion of potassium by the kidney, which can result in increased salt and water retention, increased blood volume and potassium loss. This combined with the vasoconstrictive effects of ANG II increases blood pressure.2,6-8,10
ANG II actions are mediated by AT1 and AT2 receptors.2,5-8 Most pathological cardiovascular actions of ANG II come from its interaction with the AT1 receptor.1-3,11 The negative effects of ANG II may be partially offset by AT2 receptor stimulation, which has favorable effects on vasodilation, tissue growth and repair, and cardioprotective effects.11-13
Angiotensin receptor blockers (ARBs) antagonize the actions of the RAS by blocking ANG II from binding with AT1 receptors, while preserving the positive effects mediated by AT2 receptor stimulation.1-3 ARBs lower blood pressure, modestly decrease aldosterone production, and can reverse vascular hypertrophy.1-3,9,11-13
References
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- Timmermans PB, Duncia JV, Carini DJ, et al. Discovery of losartan, the first angiotensin II receptor antagonist. J Hum Hypertens 1995; 9 Suppl 5: S3-18.
- Fyhrquist F, Metsarinne K, Tikkanen I. Role of angiotensin II in blood pressure regulation and in the pathophysiology of cardiovascular disorders. J Hum Hypertens 1995; 9 Suppl 5: S19-24.
- Oparil S, Williams D, Chrysant SG, Marbury TC, Neutel J. Comparative efficacy of olmesartan, losartan, valsartan, and irbesartan in the control of essential hypertension. J Clin Hypertens (Greenwich) 2001; 3 (5): 283-291, 318.
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- Lemarie CA, Paradis P, Schiffrin EL. New insights on signaling cascades induced by cross-talk between angiotensin II and aldosterone. J Mol Med (Berl) 2008; 86 (6): 673-678.
- Mehta PK, Griendling KK. Angiotensin II cell signaling: physiological and pathological effects in the cardiovascular system. Am J Physiol Cell Physiol 2007; 292 (1): C82-97.
- Heran BS, Musini VM, Bassett K, Taylor RS, Wright JM. Angiotensin receptor blockers for heart failure. Cochrane Database Syst Rev 2012; (4): Cd003040.
- Pimenta E, Gaddam KK, Pratt-Ubunama MN, et al. Aldosterone excess and resistance to 24-h blood pressure control. J Hypertens 2007; 25 (10): 2131-2137.
- Dell'Italia LJ. Translational success stories: angiotensin receptor 1 antagonists in heart failure. Circ Res 2011; 109 (4): 437-452.
- Unger T. The role of the renin-angiotensin system in the development of cardiovascular disease. Am J Cardiol 2002; 89 (2a): 3A-9A; discussion 10A.
- Ferrario CM. Cardiac remodelling and RAS inhibition. Ther Adv Cardiovasc Dis 2016; 10 (3): 162-171.
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